title: Amphiphilic peptide-loaded nanofibrous calcium phosphate microspheres promote hemostasis in vivo.
abstract: Most fatalities from trauma occur due to severe blood loss. There is a need for improved hemostatic biomaterials that can address this problem. The aim of this study was to determine the in vivo efficacy of nanofibrous microspheres (NFM) loaded with hemostatic peptides, specifically ideal amphipathic peptides (IAP) that have been demonstrated to possess both procoagulant and antifibrinolyic activities. We demonstrate that IAP can be coupled to NFM (IAP-NFM) to form matrices that exhibit substantial hemostatic activity. IAP-NFM matrices were compared to a commercial zeolitic hemostatic biomaterial (QuikClot) and have superior efficacy in reducing bleeding in vivo. In both a murine tail transection and a murine hepatic injury model, bleeding times were significantly reduced (P<0.05) with the use of IAP-NFM as compared with equal masses of either QuikClot or NFM alone, or no treatment. Importantly, histological examination revealed no tissue injury when IAP-NFM or NFM were applied to hepatic lacerations. In contrast, QuikClot caused widespread hepatocyte degeneration and necrosis, with higher average injury zone thickness as determined by semiquantitative analysis. In summary, NFM was able to maintain the pro-coagulant properties of IAP in our preclinical model, caused no observable tissue damage at the site of application and had better performance than QuikClot controls.
authors.affiliation: Lady Davis Institute for Medical Research, Department of Medicine, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
authors.forename: Jianqiu
authors.initials: J
authors.lastname: Wu
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Lemarié
authors.forename: Jake
authors.initials: J
authors.lastname: Barralet
authors.forename: Mark D
authors.initials: MD
authors.lastname: Blostein
mesh_terms: D000327:Adsorption; D000818:Animals; D002130:Calcium Phosphates / Q000737:chemistry*; D005170:Factor X / Q000378:metabolism; D006487:Hemostasis / Q000187:drug effects*; D006490:Hemostatics / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008863:Microspheres; D057139:Nanofibers / Q000737:chemistry*; D010455:Peptides / Q000494:pharmacology*; D013501:Surface-Active Agents / Q000494:pharmacology*; D013623:Tail
chemical_list: D002130:Calcium Phosphates; D006490:Hemostatics; D010455:Peptides; D013501:Surface-Active Agents; D005170:Factor X; C020243:calcium phosphate
keywords: Amphipathic peptide; Amphiphile nanofiber; Hemorrhage; Microsphere; Trauma